JPH0340328B2 - - Google Patents

Description

[Detailed description of the invention]

In GPC (gel permeation chromatography) and HDC (hydrodynamic chromatography), the peak composition is estimated from the elution volume in order to quantify the molecular weight or particle size of separated particles. Elution volume is quantified in chromatography by measuring the transit time of undisturbed markers to a detector and relating the position of the solute to the position of the marker. Even liquid chromatography pumps with excellent properties generally do not have a flow stability of 0.3% or more in repeated analyses, so it is typical to use markers. For this,
If elution times are measured assuming a constant flow, measurements of latex particle size often result in unacceptable errors, as shown in the Examples. In liquid chromatography (LC), concentration-sensing detectors (ultraviolet = UV, infrared = IR, refractive index =
Another source of flow-related errors (RI, conductivity) is that there is an inverse proportional relationship between peak area and flow rate, e.g., a 0.5% decrease in flow increases area by 0.5%. What causes the flow to become unstable is the instability of the peak width over a certain period of time, which causes the individual peak areas to fluctuate. Such instabilities, for example in reciprocating piston pumps, tend to vary from one pump stroke to the next due to the degree of leakage of the check valve, and where the stroke volume is typically 50 to
This occurs because it is 500 microliters (μ). Current methods of measuring flow through are somewhat complex, such as collecting the eluent in a graduated cylinder and measuring the movement of an air bubble injected into the flow, or accumulating the total number of dumps in a siphon-on dump counter. Includes all techniques that are inaccurate or unstable. Other classic flow measurement devices, generally for a wider range of liquid flows, are: 1 Coriolis flowmeter. This measures most of the flow as a rotational torque force relationship. This method is complex and expensive. Accuracy is ±0.4%. 2 Ultrasonic flow meter. This is suitable for flows per gallon per minute. Accuracy is ±0.5
%. 3 Differential pressure (D/P) flow meter. Measures the drop in pressure through an orifice, and this cell is prone to clogging and accumulation, and is affected by viscosity. 4 Turbine meter. target meter. bench urimeter. rotor meter. Pitot tube. All of these are used in principle for flow rates of 50 c.c./min or higher. 5 Continuous heating flow meter. This heats the eluent and continuously measures the downstream temperature. The results will vary due to variations in the specific heat of the liquid being measured and the ambient temperature. 6 Self-heating thermistor. The cooling is proportional to the flow and is not constant; the results vary due to changes in the specific heat of the solution and the ambient temperature. The present invention has an accuracy of ±0.1 under typical LC conditions.
This invention relates to an excellent liquid measuring method and apparatus for measuring liquid movement in %. In particular, the present invention satisfies the technology required for an improved liquid measuring method and device for accurately measuring liquids of 0.1 to 10 c.c./min, where measurement accuracy is extremely important. be. The method and apparatus of the invention operate in a self-heating manner, e.g. by injecting a heating pulse into the flowing stream via a small thermistor (or semiconductor), e.g. a microprobe or a fast response thermistor. This method uses the principle of detecting downstream pulses. Pulse detection controls the next upstream heat pulse. This process is repeated. The important key points to achieve this technique of measuring flow are, in particular: 1. Minimize the amount of heat in the heating “pulsar” and “sensor” by applying semiconductor pulse and sensor elements; 2. Eliminate ambient heat bias and shorten the response time for subsequent pulse detection. 3. utilize a flow measurement scheme with highly accurate flow measurements and improved methods for flow cell validation; and 4. To establish a flow cell and method which, by selection and operation, are completely independent of variations in temperature and liquid composition. The general principle of heated pulse injection is not entirely new for liquid measurements, and the Utopia Instrument
“Knauer” by Joliet, Illinois of Company
None of the above-mentioned technical improvements (1-4) have been embodied in conventional liquid flow meters, although they have been previously applied in the form of what is known as "Electronic Volumeter". As seen in the literature, the main difference in utility between the present invention and conventional flow meters is the establishment of a better two-probe measurement flow cell (Knauer teaches utility only for a four-probe device). The present invention has the further advantage of measuring water-soluble solvents, a utility not described by Knauer. (b) resistive heatable means operably disposed within said passageway for generating successive pulses of heat to a liquid flowing within said passageway; and (c) said heating means within said passageway. (d) a heat sensitive means for sensing the temperature of the liquid, operably disposed in a spaced relationship downstream of the resistive heat means; and (d) electronically measuring the time between successive sensed heat pulses. a flow cell for measuring the volumetric flow rate of a liquid, the resistively heatable means comprising a semiconductor 26, the heat sensitive means comprising a heat sensitive semiconductor 28, The means for electronically detecting the time between pulses includes a rate-of-change sensing circuit 74 for generating a signal C, the magnitude of which is proportional to the rate of change of the resistance of the heat-sensitive semiconductor with respect to time. The rate-of-change sensing circuit 74 is connected to operate a timer circuit 118 that applies successive current pulses to the heating semiconductor in response to the electrical signal. The invention also includes the steps of: (a) transporting the liquid to be measured through a flow cell that includes a body forming a passage; and (b) sequentially applying heat pulses of a fixed length to the liquid. (c) detecting the temperature of the liquid using downstream sensing means, the method comprising: a semiconductor disposed at a first fixed location in the passageway; applying the thermal pulse to the liquid using the heating semiconductor; detecting the pulse from the heating semiconductor using a thermal semiconductor disposed downstream from the heating semiconductor at a constant interval; operative to detect a temperature change within the liquid; and generating an electrical signal from the temperature dependent signal of step (C) indicative of a linear or higher order rate of change over time of the sensed temperature change. applying subsequent heat pulses using the temperature change rate signal to create a condition where the pulse frequency is related to the volumetric flow rate of the liquid; and detecting the time between pulses. The method is characterized in that it includes the following steps. A preferred embodiment of the invention consists in the use of self-heating thermistors as thermal pulse elements in combination with rapid response thermistors as thermal sensors, each thermistor surrounding a semiconductor thermistor element. For example, an electrical insulator such as glass. Furthermore, a similar second time-induced version of the resistance of a heat-sensitive thermistor is applied as a signal to pulse the self-heating thermistor. According to the method of the invention, other known electronic flow cells (i.e. the measurement principle of a "flow cell" is based on the flight time of an electron injection heating pulse) are operated in a manner that produces an improved amount of flow. be able to. However, optimal operation with the present invention is possible by using the flow cell of the present invention. As used herein, the term Newtonian liquid refers to a liquid whose viscosity is substantially constant under the measured flow conditions. Although the present invention has been described in terms of applications where real data is required, such as representing instantaneous or average flow rate or total flow capacity as a flow quantity, it may also be used, for example, to adjust the flow to a measurement set. By continuously detecting the flow rate and transmitting a signal (flow amount) to the pump, it can also be applied to control methods and devices for adjusting pumps for chromatography and other liquid measurement. . Furthermore, although the technical need for an improved device and method for measuring flows less than 10 c.c./min has been described so far, the principle of the present invention is quite similar as shown in Example 3. It is obvious that it can also be applied to measure large flow velocities. Features of the invention are apparent from the accompanying drawings, "Detailed Drawings of the Invention": FIG. 1 is a cross-sectional view of a preferred flow cell for liquid measurement according to the principles and spirit of the invention; FIG. 2 is a top view showing the cell section of the flow cell of FIG. FIG. 3 is a preferred electronic circuit diagram for operating a flow cell according to the principles of the present invention. FIG. 4 is a correction graph of the flow cell as shown in Example 1. 1 and 2, a preferred embodiment of the apparatus of the present invention shows the actual movement of the measuring liquid (here 0.1 to
10 c.c./min). The flow cell 10 consists of a body 14 having a flow passage through which the measuring liquid flows. The size or internal volume of the (calibrated) flow cell is constant and ranges from 0.01 to 0.5 cc, preferably from 0.01 to 0.25 cc. A thermistor 16 (or the same as described below) is attached to the body 14 and extends into the passageway, and is adapted for use in a self-heating manner to deliver short, sharp pulses of heat to the liquid to be measured. It is being The self-heating thermistor has a heating surface 18 exposed in the passageway for direct contact with the measured flow liquid. Preferably, the heating surface is located in the center of the passageway. At a distance from the self-heating thermistor is a second thermistor 20, which is a quick-acting thermistor, preferably slightly smaller, and is made to be heat sensitive. The thermal thermistor has a thermal surface 22 and extends into the passageway 12 (downstream from the self-heating thermistor) for direct contact with the measuring flow liquid. A thermal thermistor is also preferably located in the center of the passageway. The preferred self-heating thermistor used is a "standard probe" thermistor, which is of various commercially available types known in the relevant art. These standard probe thermistors have a glass ball or probe 24 that is the heating surface of the thermistor. A semiconductor element 26 is housed inside the glass probe and is electrically insulated so as not to come into direct contact with the measuring liquid. The diameter of the thermistor probe 24 is 0.254 cm (0.100 inch). This is used to maintain a pulse force of about 50 to 150 milliwatts without degrading or changing the electrical properties even during long-term use. A probe with a low heating value, as indicated by a time constant ratio (TC) in air of 14 to 22 seconds, is generally satisfactory for providing a fast enough pulse to the liquid and is amenable to the application of the present invention. The power of this pulse, along with the heat sensitivity of the thermistor 20, is sufficient to produce a heat sensitive pulse. Thermal thermistor 20 is a "quick response" glass probe thermistor, consisting of a semiconductor element 28 encased in glass 30. thermistor 2
0 is of lower calorific value and has a TC ratio in air of 5 seconds or less. Commercially available thermal thermistors commonly described have a negative temperature coefficient of 3-4%/°C. This range of sensitivity is entirely suitable for use in the present invention. Even if the temperature coefficient of a thermal thermistor is small, it can still be operated as long as a sufficient resistance change is sensitive to and recorded by the thermal pulse of the liquid. The heating coefficient of a self-heating thermistor is not a very important parameter since the thermistor is used in a self-heating form.
However, in order to minimize the possibility of failure of the thermistor due to inadvertent overheating, for example if the device is handled improperly, self-heating thermistors with a negative temperature coefficient should be used. is preferred. However, a thermistor with either a positive or negative temperature coefficient can also be used as a thermal thermistor. The present invention also contemplates the use of devices similar to self-heating thermistors. These are based on the substitution of a semiconductor-based heating element for the thermistor element 16, which differs in that it does not have the temperature coefficient characteristic that characterizes thermistor element. The term "semiconductor" refers to a resistance of 10 ³ to 10 ¹³ micro-ohm centimeters, preferably 10 ⁴
It defines a substance that is ~10 ⁶ micro-ohm-centimeter. Useful as element 26 is a resistive heating element whose resistance is in the transition range between conductor and semiconductor, i.e. 750
~1000 micro-ohm-centimeter. As used in this disclosure, the term "semiconductor" is defined to include the latter materials (e.g., certain carbon-based materials) having a resistance within a certain transition range, which is the subject of the present invention. It is suitably incorporated into a resistance heating device useful for the purpose. A feature of the flow cell 10 of the present invention is that it is simple in design and construction.To fabricate the cell portion 14, the flow cell is preferably constructed using glass-containing Teflon in building blocks. The passage 12 can be created using a common drilling method. Threaded apertures 32, 34 are provided at both ends of the cell section for connection of the passageway 12 with end fittings 36, 38 of the chromatography tube for the liquid to be measured flowing through the passageway 12. Similar threaded apertures 40, 42 are provided in the cell portion perpendicular to passageway 12 in communication with each thermistor 16, 20. Because the self-heating thermistor 16 is relatively large, or the heating surface 1 of the probe 16
In order to create a space for the lower end of the cell part 8, a shallow hole-like extension 44 is provided in the lower extension of the cell passage. This extension 44 is used to center the heat-generating surface of the self-heating thermistor on the axis of fluid flow in the passageway 12 and to align it with the heat-sensitive surface 22 of the thermistor 20 (thermal thermistor (also preferably located in the center of the axis of the passage), allowing for adjustable movement. If the thermistors are of different sizes, the flow passages may be expanded at either or both of the thermistors 16 and 20 so that the heat-generating and heat-sensitive surfaces of the thermistors are aligned with the center of the passage axis. It can create a coaxial expansion space. By attaching thermistors 16 and 20 on opposite sides of the cell section 14, a small flow cell can be created. Thereby, a flow cell design substantially similar to that shown can be used to create a smaller and shorter flow path. Preferably, plugs 46, 48 are used which have threaded holes, preferably in plastic, located through the thermistors 16, 20 of the cell portion 14. The lead wires of the thermistors 16 and 20 are passed through this plug. The threaded openings 40, 42 are fitted with elastic O-rings 50, 52, respectively.
) is attached, and each thermistor part is pressed with a plug to form a liquid seal. A terminal piece (not shown) can be attached to the cell part using, for example, a screw. The leads of the thermistor can also be secured to the terminal strips, for example by means of standard electrical constant screws. It is clear that considerable improvements can be made to this simple cell design without changing its functionality. For example, the cell section can be made from several connecting parts (eg, each block section shown can be reversed). Furthermore, a small diameter plastic tube, for example, can also be used for the self-flow channel (aspect described in Example 3). A flow restrictor 56 is connected to the opening 34 of the flow cell 10 by an end joint 38 . The flow restrictor suitably comprises a capillary tube of suitable length to create a reasonable back pressure to restrict liquid flow and prevent minimal outgassing of the liquid to be measured. Flow restrictors are advantageously used when the flow cell is placed at insufficient back pressure to prevent deleterious outgassing events. Any device such as a conventional restrictor valve can be used in place of the capillary tube described above. When a flow restrictor is used in conjunction with the flow cell 10, for example to convey the effluent of a chromatography column, the accuracy of the liquid measurement is sometimes at its highest level (at extremely low back pressures). (The degree of degassing of the measured liquid increases). A preferred design electronic circuit for operating the flow cell 10 is as shown in FIG.
Consists of. Circuit 58 consists of a standard voltage distribution circuit consisting of potentiometer 60 and series resistor 62 distributed at junction A from thermistor 20 and series resistors 64,65. The total resistance of the circuit is sufficient to create negligible current pulses by pulsating the resistance drop of the thermistor, thus not producing harmful self-heating of the heating thermistor. A typical power source terminal is connected to a voltage distribution circuit to provide an input voltage within the equilibrium range of the thermistor 20. Capacitor 67 stabilizes the temporarily abrupt voltage at junction A to within the positive voltage supply level. Pulsed temperature changes in the liquid to be measured are electronically sensed in the form of positive voltage pulses that are proportional to the change in resistance of the thermistor 20 with the change in temperature (this circuit does not support the use of a thermal thermistor with a negative temperature coefficient). (assumed to be the purpose). After the generated voltage pulse passes through the coupled current limiting resistor 66, it is inverted by a factor of 50 due to the selected resistance ratio of the resistors 70 and 72.
inverting) amplifier 68. Resistors 70, 72 are connected to the negative feedback of amplifier 68 in a voltage divider circuit (as a standard arrangement). Typical pulse waveforms of pre-amplified voltage pulses and amplified voltage pulses are shown in A to B.
It is illustrated as . This pulse is preferably fed to a two-stage differential amplifier circuit 74, 74a.
A first stage differentiator circuit 74 is connected in series with a current limiting resistor 78 and to an inverting input of an operational amplifier 80. Feedback register 82
returns the input signal to zero according to each pulse signal. Cavacitator 84 is connected in parallel with resistor 82 to filter out high frequency ambient electrical noise. The pulse signal from amplifier 80 is inverted and proportional to the time rate of this pulse change (A-B), as shown in Pulse C. Since the amplified (A-B) voltage pulse is proportional to the electrically sensitive resistance of the thermal thermistor, the pulse produced by the amplifier 80 (C) is proportional to the change in pulse temperature of the liquid being measured and the resistance change of the thermistor 20. Equivalently considered as the time fraction of the amplified change (or due to the initial time induction). The time ratio of the changing pulse signal is guided to the second stage differentiating circuit 74a. The circuit consists of conventional elements (with amplifier 80), which give similar reference numbers. Additionally, the uninverted input of the second stage amplifier 80a is provided to a nulling bias circuit 84 connected to the input to condition the output of the voltage pulse signal of the amplifier 80a. The outline of the amplifier 80a output is illustrated in Figure D, which shows the pulsed temperature change of the measuring liquid and the amplified, electronically induced second temporally induced version of the thermal thermistor 20 resistance. It is. A second induced voltage pulse is provided through current limiting resistor 86 to the uninverted input of operational amplifier 88 . This amplifier is connected to a capacitor 90 and resistors 92, 94 to produce large amplification with associated high frequency overload. The output signal is thus amplified, for example by a factor of 500, and then passed through a small pass-through consisting of a resistor 96 and a capacitor 98 produced by an amplifier 88 and connected to a conventional power supply. The total amplification and total induction function is E
A voltage pulse with a square waveform as shown in the figure is generated. The voltage pulse of Figure E is provided to a timer circuit 100 to pulse a self-heating thermistor. This circuit includes a current limiting resistor 102 and also connects the base of a conversion transistor 104 to convert the collector terminal 106 from +15 volts (power supply level) to zero upon arrival of the output of each voltage pulse of Figure E. It is connected to the. By organizing the voltage pulses at the collector terminal 106, the voltage pulses range from 0 to +15. At rest, the collector is biased to +15 volts by a voltage distribution circuit consisting of resistor 108 and switching transistor 104. Second voltage divider 1
10,112 produces a high positive voltage level. These two voltage generators are arranged to pass through the capacitor 114 so that both plates have a high voltage. When the collector terminal voltage switches, it causes the capacitor 114 voltage to drop rapidly. Thereby, the capacitator plate 11
6 is biased to zero for a short time until the second divider returns to its original voltage level. As a result, the width of the voltage pulse produced at the collector terminal is reduced to a voltage peak that is applied to pin #2 of timer 118, which is the time cycle reset pin. The timer produces a voltage pulse at pin #3, the duration of which is determined by a variable resistor 120 in conjunction with a capacitor 122 connected to pins #6 and #7. Its time interval is 0.01~1.0
Adjustments can be made in this circuit in seconds. Pins #1 and #8 are connected in common and each supply power is +15 volts. The output voltage for a period of time is supplied from pin #3 to relay 124, which is a double pole and single throw relay for the purpose of power supply, contact between series resistor 126 and heating thermistor 16. The relays are connected by leads 128, 130 to an external data collector 132, such as a computer for recording each active point of a self-heating thermistor (to derive T). The circuit is first activated by manual switch 134. Single 100ma ±15
A volt regulated power supply is used to operate the entire circuit. The liquid measurement process is initiated by activating the Rh (self-heating thermistor) heat pulse push button. A thermal thermistor (Rt) with a temperature coefficient of 4%/°C produces a positive voltage at junction A as a slow heat pulse passes through the sensitive zone. After this signal is amplified in B,
It passes through the capacitor 76 and is connected to the conversion input of the amplifier 80 of the first stage differential amplification circuit 74.
In this circuit the amplification inversion produces a voltage pulse at C which is equal to the temporally induced one at B. The output at c is proportional to dRt/dt, so for small temperature changes there is a virtually zero response to the heat pulse produced by the self-heating thermistor. A single induced pulse output returns to baseline too slowly to be optimally created for subsequent pulses. The second stage amplifier 80 thus produces the approximate pulse output shape shown in Figure D.
Most preferred are those which yield a converted second derivative in a. This is d ² R/
Proportional to dt ² . This voltage pulse form is amplified at E and sent to a transistor time circuit which applies power to the read relay. This relay connects both the pulse counter (i.e. computer) and the self-heating thermistor 16 for a fixed amount of time (typically 0.1 to 1.0
seconds) provides a pulse of 30 volts DC. Measurement accuracy is improved by using a DC pulse form as opposed to an AC voltage pulse to the heating thermistor 16. A 2K ohm resistor 126 protects the self-heating thermistor from self-heating and overheating which would reduce its resistance. When using 30 volts DC with a standard probe thermistor, Rh
According to the calculation, a maximum power of 113 mW is consumed. The velocity of the flow of the measuring liquid and/or the total flow is calculated electronically based on the pulse data collected by the electronic circuit and calculated from the following general formula: T=Vc/r+K {where T= time between pulses (eg, sec); Vc = calibrated cell capacity constant (eg, cm ³ ); f = flow rate (eg, cm ³ /sec); K = calibrated time constant (eg, sec). } The values of Vc and K can be determined, for example, by the flow cell correction procedure described in Example 1. T is the collected pulse time data and f is the measured flow rate of the measurement liquid. Since the Vc/f value has been shown to be well linearly related to T over a wide range of flow rates (see Example 1), the calculation of f can be done electronically and in the desired manner. A visual chart recorder or other device displays the instantaneous and/or average flow rate, or the total flow of the liquid to be measured over any elapsed time is measured in total flow pulse counts (ΣT). It can be expressed based on Example 1 This example describes a suitable and preferred correction method for determining correction constants Vc and K. These constants are described with respect to a given flow cell, electronic circuit, and device. In this study, the flow cell has thermistors 16 and 20 placed approximately 1 1/2 inches (3.8 mm) apart (located center to center) and has a diameter of approximately 1/16 inch (0.159 cm). used in the flow tube 12 of
It's the design. Timer 118 is set for a pulse heating time of 0.8 seconds. Potentiometer 60 is adjusted to provide a positive baseline voltage of 50 mV at steady state when the heating thermistor pulses with positive charge. The zero adjustment bias circuit is adjusted so that the voltage becomes zero at D when there is no pulse. The equipment used to calibrate the flow cell consists of a metering pump manufactured by LDC Corporation. A pump pumps the liquid (water) from the chromatography storage tank, and using a chromatography tube with a standard outer diameter of 1/16 inch (0.159 cm), the liquid is continuously pumped at a predetermined flow rate using a pressure gauge and pulse humidification. It flows through the coil and finally into the flow cell. The discharge from the flow cell is a back pressure-applied capillary coil [3 inches x 0.005
(7.62 cm x 0.127 inch) inner diameter capillary tube] into a collecting vessel. A highly accurate timer is used to ensure the flow rate of the liquid. The data are shown in Table 1. In the table, f is the average flow rate (cc/
min), T is measured from relay 124,
It is the average time (sec) between pulses of a self-heating thermistor.

[Table] Correction constants Vc and K can be calculated using two equations in which f and T are extracted from the two data in Table 1 and substituted into the equation T=Vc/f+K, respectively. The correction cell capacity Vc is 0.048cc, and the correction constant K is 0.63sec. Therefore, the flow rate (cc/sec) through this flow cell can be measured using the formula Tsec=0.048cc/f+0.603sec. The calculation of the above equation can be made easier by creating the graph shown in FIG. Create a straight line (gradient of Vc) from the data points of many solutions at many Tsec and fc.c./min. Moreover, this straight line crosses the vertical axis at the K value. Therefore, the equation shows a good agreement with the line y=mx+b relationship. The correlation coefficient for this data is
It is 0.99989. Using the above formulas to correct the flow cell constants, exceptionally accurate liquid measurements can be made as shown in Example 2. Nevertheless,
Liquid flow can also be measured using flow cells with conventional correction methods. For example, by averaging the total pulse number and pulse frequency data from relay 124 for a known accumulation volume or flow rate. These latter correction methods can be applied, for example, to use flow cells for accurate measurement of non-Newtonian liquids. Example 2 The accuracy of an electronic flow cell of the same design as that used in Example 1 was demonstrated when the cell was passed through a 5 ft (1.524 m) chromatography tube with a standard 1/16 inch (0.159 cm) outer diameter and It was investigated by connecting to the effluent storage tank mentioned above. 6 inches (15.24
Water was fed by gravity feed through the flow cell under a hydrostatic head pressure (total) of water (cm). The water was finally drained into the collection container through a tube (1/16 inch (0.159 cm) outside diameter) with one end immersed in the water in the collection container. The initial liquid flow was approximately 1 c.c./min and decreased slightly during the experiment. The time value of each pulse T produced by relay 124 was stored electronically in the memory bank of the microcomputer. When the data collection was completed, the computer electronically generated a linear regression curve, and the standard deviation of T was calculated to be 2.973 milliseconds. The measured standard deviation was calculated to be 0.092% with a confidence limit of 63% (±1 sigma). The observed accuracy is determined to be no worse than 0.092% in this experiment since the actual flow appears to have varied randomly (very slightly) only due to imperfections in the performance of the test equipment. .
Just as true accuracy is even better. Example 3 Many of the flow cells used in this experiment differed substantially only in corrected cell capacitance (Vc). The inner diameter of flow cells No. 1 and No. 2 in Table 2 is
0.031 inch (0.79mm) each 24 inches (61
cm) and 12 inch (30.5 cm) tubing connected between each individually thermistor mounted flow cell block.
These are relatively large capacity cells. Cell No.3
and No. 4 are slightly smaller capacity cells of the design shown in FIGS. 1 and 2. Flow cell No. 3 is the one used in Example 1. Various liquid chromatography measurement pumps were used to determine the dynamic flow range specific to each cell design. The results are shown in Table 2.

[Table] Large capacity cell No. 1 shows the minimum flow detection limit at approximately 10c.c./min. This upper limit was not tested due to the limitations of the pump equipment used in the test. This flow cell uses the liquid flow measurement principle of the present invention at 10c.c./
This shows the possibility of expanding to measurements of flow velocities considerably greater than min. All of flow cells No. 1 to 3 are practically 10c.c./
This demonstrates the utility of the present invention for measuring liquids over the entire practical range of flows up to min. This test is not intended to be construed as seeking an optimal flow cell dynamic operating range for any given cell design used in the test. What should be noted here is that the K values determined by flow cells No. 1 to No. 4 are not the same.
The slight difference between the K values determined is likely due to small differences in the electrical characteristics of the thermistors 16, 20 of each flow cell. Even if the flow cells are of similar manufacture and components, it is conceivable that their heat capacity and/or electrical properties may be slightly different.

[Brief explanation of drawings]

FIG. 1 is a cross-sectional view of a preferred flow cell for liquid measurement in accordance with the principles and spirit of the present invention. Second
The figure is a preferred electronic circuit diagram for operating a flow cell in accordance with the principles of the present invention. Figure 3 shows Example 1
This is a correction graph of the flow cell as shown in FIG.

Claims (1)

[Scope of Claims] 1. (a) a flow cell body defining a passageway for transporting a liquid to be measured; (b) operatively disposed within said passageway and configured for liquid flowing within said passageway; (c) resistive heatable means for generating successive heat pulses; and (c) temperature of a liquid operatively disposed in a spaced relationship downstream of said resistive heatable means within said passageway. (d) means for electronically detecting the time between successive sensed heat pulses, the flow cell for measuring the volumetric flow rate of a liquid, comprising: The resistive heatable means includes a semiconductor 26, the heat sensitive means includes a heat sensitive semiconductor 28, and the means for electronically detecting the time between successive heat pulses includes a rate of change sensing circuit for generating a signal C. 74, wherein the magnitude of the signal C is proportional to the rate of change of the resistance of the heat-sensitive semiconductor with respect to time;
The rate of change sensing circuit 74 is connected to operate a timer circuit 118 that applies successive current pulses to the heating semiconductor in response to the electrical signal. 2. The flow cell of claim 1, wherein the passageway has a calibrated volume (Vc) of 0.01 to 0.5 milliliters. 3. The resistively heated semiconductor is adapted to operate in a self-heating mode, and the heat sensitive semiconductor is a fast response thermistor having a smaller mass than the resistively heatable thermistor.
The flow cell according to item 1 or 2. 4. The flow cell according to claim 1, 2 or 3, wherein the semiconductor is protected and insulated so as not to come into direct contact with the liquid to be measured. 5. The flow cell of claim 4, wherein the semiconductor is encapsulated within a glass insulator and disposed substantially centrally within the passageway. 6. Claims 1 to 5, wherein the heat-sensitive semiconductor has a time constant in air of less than 5 seconds, and the resistive heating semiconductor has a time constant in air of less than 22 seconds. Flow cell described in any of the sections up to. 7. A flow cell according to any one of claims 1 to 6, including flow restriction means in communication with the passageway for applying back pressure to the liquid being measured. 8. Any one of claims 1 to 7, wherein the passage has a size suitable for measuring a volumetric flow rate of less than 10 c.c./min of liquid. The flow cell described in . 9. (a) transferring the liquid to be measured through a flow cell that includes a body forming a passageway; (b) sequentially applying heat pulses of fixed length to the liquid; and (c) detecting the temperature of the liquid using downstream sensing means; is added to the liquid, and a pulse from the heating semiconductor is detected using a heat-sensitive semiconductor disposed downstream from the heating semiconductor at a constant interval, and the heat-sensitive semiconductor detects the temperature within the liquid. generating from the heating-dependent signal of step (C) an electrical signal responsive to the rate of change of the sensed temperature change over time; applying subsequent heat pulses using the rate of temperature change signal to create a condition related to flow rate; and detecting the time between pulses. 10. The method of claim 9, including the step of providing a flow rate of the liquid to be measured in a range of less than 10 c.c./min. 11. said passage has a volume equal to a calibrated volume (Vc) ranging from 0.01 to 0.5 cc;
A method according to claim 9 or 10. 12. the heating semiconductor is a thermistor operating in a self-heating mode, the heat-sensitive semiconductor is a fast-reacting thermistor having a mass smaller than the mass of the resistive heating semiconductor, and the generation of the thermal pulse is an electrical pulse differentiated with respect to time. as claimed in claim 9, 10 or 11, wherein the pulse is a time-differentiated response of the heat-sensitive semiconductor to a pulse of temperature change of the liquid to be measured. the method of. 13. The method of claim 12, wherein the activated electrical pulse response is at least equal to the second derivative of the electrical pulse response of a thermal thermistor with respect to the pulsed temperature change of the liquid being measured. 14. The method according to any one of claims 9 to 13, comprising supplying the effluent of the flow cell through a flow rate restriction means. 15. Claim 10 includes the step of encapsulating and protecting the semiconductor to prevent direct contact between the semiconductor and the liquid to be measured.
The method described in any of paragraphs 1 to 14.